The highest rate of protein catabolism ever reported for surgical patients is found in neonates on extracorporeal life support (ECLS). Methods to limit this process remain sparsely investigated despite the close linkage between protein loss and increased morbidity and mortality in surgical patients. This proposal seeks to test the hypothesis that the intravenous administration of insulin will ameliorate the extreme protein catabolism noted in neonates on ECLS. Such an investigation is of importance as ECLS is a demonstrated lifesaving surgical therapy that has been utilized in over 16,000 babies with respiratory failure. However, morbidity remains high and the attendant mortality has stayed constant at 15-20 % over the past decade. A two-center, prospective, randomized, crossover trial is proposed using neonates on ECLS as a model of neonatal critical illness and employing validated, state of the art, stable isotope tracer techniques to quantify protein metabolism. The protocol is designed to determine if the application of a hyperinsulinemic euglycemic clamp in parenterally fed neonates on ECLS will result in an improvement in protein balance, and to elucidate the mechanisms by which the change occurs. This fundamental metabolic investigation has the potential to improve the management of neonates requiring ECLS and is important in defining how net protein balance may be optimized in all critically ill surgical neonates.